Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged ≥80 years

Abstract

Objective

It has been reported that aspirin and other non-steroidal anti-inflammatory drugs (NSAID) may protect against dementia of Alzheimer's type and/or vascular dementia. However, co-morbidity and the dose of aspirin may be critical. A major indication for low-dose aspirin is prophylaxis after stroke and transient ischaemic attacks, conditions that may obscure an anti-dementia effect by the drug. Alternatively, low-dose aspirin may be insufficient if the protective effect is due to an anti-inflammatory mechanism. The aim of this study was to assess whether high-dose or low-dose aspirin may protect against Alzheimer's dementia in subjects aged ≥80 years. For comparison, effects of (other) NSAID, paracetamol and d-propoxyphene were studied.

Methods

Global, cross-sectional, and longitudinal (1991–2000) epidemiological analyses of clinical, cognitive and drug treatment data on 702 individuals 80 years old or more (351 twin pairs of same sex), all alive at inclusion: mean age 83.9 years (80–99 years). Calculations were made with logistic regression of associations between use of various analgesics and cognitive function, after adjustment for age, gender, and cardiovascular and cerebrovascular diseases.

Results

Users of high-dose aspirin had significantly lower prevalence of Alzheimer's dementia and better-maintained cognitive function than non-users. There were numerically similar but not significant associations with use of low-dose aspirin and other NSAID. There were no such associations with use of either paracetamol or d-propoxyphene.

Conclusion

Aspirin might protect against Alzheimer's disease, but controlled trials are warranted.

Appendices

Appendix 1

Evaluation of cognitive status and dementia in the OCTO Twin Study

A rating of cognitive status (Cognitive Rating, CR) was conducted on all subjects using the scale below. The CR represents a composite score and was used as a convenient way to summarise performance across the tests and to provide an evaluation of the person's overall memory and cognitive function, taking overall health and functioning into account.

• 1. Intact—"normal"—memory and cognitive functioning (corresponding MMSE ≥26), sensory and motor function, overall health, and physical functioning were taken into account

• 2. Mild dysfunction/questionable impairment: evidence of compromised memory and/or cognitive functioning, not meeting DSM-III-R criteria for dementia

• 3. Mild impairment/dementia: meeting behavioural criteria for mild dementia [20]

• 4. Moderate impairment/dementia: meeting behavioural criteria for moderate dementia DSM-III-R criteria [20]

• 5. Severe impairment/dementia: meeting behavioural criteria for severe dementia [20]

The CR was based on a thorough review of memory and cognitive performance. The test battery encompassed:

• 1. Orientation to own person (name, year of birth, current age)

• 2. Self-ratings of memory and thinking (six questions)

• 3. The Mini-Mental State Examination (MMSE), [14]

• 4. The Information Test (A Swedish version of the WAIS Information Task [21]

• 5. Figure Logic/Inductive Reasoning (SRB:2) [22]

• 6. Block Design—Koh's Block Test ( SRB 3) [22]

• 7. Verbal Meaning—Synonyms (SRB 1) [22]

• 8. Digit—Symbol (A modified version of the speeded Symbol-Digit Substitution Test from the Wechsler Adult Intelligence Scale, WAIS, where subjects were instructed to give a verbal response, instead of a written) [23]

• 9. Digit—Span, Forward and Backward test (WAIS) [23]

• 10. Perceptual Speed—Psif [22]

• 11. Thurstone's Picture Memory Test [24]

• 12. Prose Recall (A Swedish language prose recall task similar to the prose passages in the Wechsler Memory Test (WMS) [23]

• 13. The MIR Test including naming, free recall, recogntion and correspondence tasks [25]

• 14. The Swedish Clock Test (including the three subtests: clock drawing, set the hands of a wooden clock with no numbers on the face to certain standard times, and set time to certain standard times [26]

• 15. The Coin Test [26]

The CR was made in the context of the subject's overall health and physical functioning, including, e.g., sensory functioning and motor handicaps. Also, observations of test-taking behaviour and everyday functioning during the in-person testing sessions were presented and taken into account before determining a CR score. In this respect, the CR represent a clinical evaluation based on multiple sources of information.

Individuals rated with mild to severe impairment (3–5) and tentatively diagnosed as dementia or demented, were routinely given a diagnostic work-up, including a detailed interview with a key informant about memory and cognitive problems (onset, course and symptomatology), and a review of medical records. Findings were presented and discussed at a consensus diagnosis conference. Diagnoses were assigned following DSM-III-R criteria for dementia [20], the NINCDS/ADRDA criteria for Alzheimer's disease [27], and the NINDS-AIREN criteria for vascular dementia [13].

Appendix 2

Definitions and distinctions for examined diagnoses (codes within parentheses refer to ICD-10)

• Myocardial infarction (I21–22): the diagnosis requires an increase of specific enzymes in conjunction with the typical clinical manifestations and/or an ECG-pattern with specific QRS-aberrations.

• Angina pectoris (I20): prescription of nitrates is considered to be a valid evidence for the diagnosis. In cases where angina is observed in temporal connection with a myocardial infarction, only infarction is registered.

• Congestive heart failure (I50) means dyspnea and oedema referable to heart disorders, and typically treated with diuretics and/or digitalis.

• Arrhythmia (I44–49): a diagnosis of cardiac arrhythmia is determined only when medical records explicitly use arrhythmia as a diagnosis. That means that fibrillation and other rhythm disturbances in connection with ongoing congestive heart failure are not included. The chief indications are paroxysmal attacks and arrhythmia in conjunction with heart blocks or Adams-Stokes attacks.

• TIA (transitory ischaemic attack) (G45): acute neurological symptoms <24 h. Diagnosis only on the basis of medical records.

• Stroke (I61;I63–65) is accepted as a diagnosis from information in records as well as from self-reports, although the few cases diagnosed only from the latter source may include TIA attacks.

• Venous thromboembolism (I121;I180) includes deep thrombosis of lower extremities and/or pulmonary embolism.

• Peptic ulcer of stomach and duodenum (K25–26) is clinically diagnosed with fibre endoscopy or X-ray support. Self-reports are accepted as the base for diagnosis.

• Dorsal pain (M54): the diagnosis is mainly based on self-reports. In cases where the diagnosis is derived from medical records it requires a specific treatment or X-ray documented spondylarthritis. For cases in which the X-ray confirms demineralisation and/or spontaneous fractures, the diagnosis is osteoporosis (M80–81).

• Coxarthritis (M16) and gonarthritis (M17) as clinical diagnoses require an X-ray confirmation and/or surgical intervention. As for dorsal pain, coxarthritis also includes mild and less well-documented cases derived from self-reports. For gonarthritis only record information was available.